Vascular Protective Effect of Rosuvastatin in Arteriovenous Fistula

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by National Cheng-Kung University Hospital
Sponsor:
Information provided by (Responsible Party):
Lam Chen Fuh, National Cheng-Kung University Hospital
ClinicalTrials.gov Identifier:
NCT01863914
First received: February 14, 2013
Last updated: May 23, 2013
Last verified: May 2013
  Purpose

Background Arteriovenous (AV) fistula is the most common vascular access for long-term hemodialysis in the end-stage renal disease (ESRD) patients. About 25% of these patients are diabetes mellitus. However, the effects of hyperglycemia on the vascular function of arteriovenous fistula are still remained unclear. Studies have shown that blood flow in the AV fistula is significantly reduced in patients with diabetes mellitus. Diabetic patients also require a longer period of time for the maturation of AV fistula, and have slightly higher complication rate than non-diabetic patients. Statins have been widely shown to mediate several important pleiotropic effects in the improvement of vascular endothelial dysfunction, attenuation of inflammatory responses, stabilization of atherosclerotic plaques, inhibition of vascular smooth muscle proliferation, and modulation of procoagulant activity and platelet function.Our experimental studies in diabetic animals demonstrate that administration of a water-soluble statin rosuvastatin significantly improves the fistula flow, vascular function and luminal dilatation of AV fistula in diabetic rats by suppression of vascular oxidative stress and inflammatory load.

Study hypothesis The central hypothesis of this research project is rosuvastatin mediates pleiotropic protective effect on vascular endothelial function and suppresses the regional pro-inflammatory reaction in the vasculature, therefore administration of rosuvastatin during the perioperative period of creation of native AV fistulas in diabetic patients with ESRD may potentiate the vascular function and reduce the primary failure rate of AV fistulae.


Condition Intervention Phase
End-stage Kidney Disease
Diabetes Mellitus
Arteriovenous Fistula
Drug: Rosuvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Rosuvastatin in the Mobilization of Endothelial Progenitor Cells and Graft Vascular Function Following Creation of Arteriovenous Fistula in Diabetic Patients With Chronic Renal Failure

Resource links provided by NLM:


Further study details as provided by National Cheng-Kung University Hospital:

Primary Outcome Measures:
  • Primary patent rate of AV fistula [ Time Frame: 3 months after operation ] [ Designated as safety issue: No ]
    The definition of primary patency of an AV fistula is defined as successful cannulation of the fistula for first hemodialysis treatment (first dialysis session)(reference: BMC Nephrol 2013;14:79). Administration of rosuvastatin protects the endothelial function in the AV fistula and restores the blood flow rate in the shunt of diabetic patients with ESRD, thereby improves the primary patent rate and early maturation of these fistulas


Secondary Outcome Measures:
  • Composite outcome measurement of the overall shunt-related complication rate [ Time Frame: 3 months after operation ] [ Designated as safety issue: No ]
    The most commonly shunt-related complications are formation of aneurysms, failure of shunt to mature, and development of thrombosis in AV fistula (Ann Vasc Surg 2012;26:680). The occurrence of shunt-related complications usually require surgical reintervention. Administration of rosuvastatin improves the vascular function of AV fistulas in diabetic patients with ESRD, therefore reduces the overall shunt-related complication rate and the requirement for surgical re-interventions.


Other Outcome Measures:
  • Composite outcome measurement of systemic pro-inflammatory response [ Time Frame: 3 months after operation ] [ Designated as safety issue: No ]
    Systemic proinflammatory response is determined by measuring blood concentrations of MCP-1, IL-1 beta, IL-6 and TNF-alpha, and the numbers of circulating endothelial progenitor cells (EPCs). Administration of rosuvastatin is associated with reduction of the systemic pro-inflammatory response and oxidative stress (levels of proinflammatory cytokines and other mediators in the circulation) in diabetic patients with ESRD. On the other hand, administration of rosuvastatin may mobilize the bone marrow-derived EPCs into systemic circulation, and the number of these circulating endothelial progenitors may provide prognostic value to the outcomes of AV fistula.


Estimated Enrollment: 80
Study Start Date: November 2012
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo tablet contains only inactive ingredient. The placebo tablets will be taken once daily for 4 weeks (1 week before operation and 3 weeks after creation of AV fistula)
Active Comparator: Rosuvastatin
Rosuvastatin (CrestorÒ, Astrazeneca) 5mg once daily for 4 weeks (1 week before operation and 3 weeks after creation of AV fistula)
Drug: Rosuvastatin
Rosuvastatin tablet (CrestorÒ, Astrazeneca) 5 mg/d PO for 4 weeks (1 week before and 3 weeks after creation of AV fistula)

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Patients with diabetes mellitus (postprandial blood sugar >140 mg/dl)
  2. Patients with end-stage kidney disease and is proposed to undertake chronic hemodialysis
  3. Patients of age 18-60 years

Exclusion Criteria:

  1. Preoperative blood sugar level >250 mg/dl or most recent HbA1c >10%
  2. Hyperlipidemia (serum LDL >100mg/dl)
  3. Recent treatment with statins
  4. Advanced liver disease
  5. Chronic alcoholism
  6. Congestive heart failure
  7. Malignancy or hematologic disorder
  8. Pregnancy or breastfeeding
  9. Past history of creation of AV fistula
  10. Scheduled for general anesthesia
  11. Emergent operation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01863914

Locations
Taiwan
National Cheng Kung University Hospital Recruiting
Tainan, Taiwan, 704
Contact: Chen-Fuh Lam, MD, PhD    8866-2353535 ext 5348    lamcf@mail.ncku.edu.tw   
Principal Investigator: Chen-Fuh Lam, MD, PhD         
Sub-Investigator: Jun-Neng Roan, MD         
Sponsors and Collaborators
National Cheng-Kung University Hospital
  More Information

No publications provided

Responsible Party: Lam Chen Fuh, Associate Professor, National Cheng-Kung University Hospital
ClinicalTrials.gov Identifier: NCT01863914     History of Changes
Other Study ID Numbers: 101-2314-B-006-045
Study First Received: February 14, 2013
Last Updated: May 23, 2013
Health Authority: Taiwan: Institutional Review Board

Keywords provided by National Cheng-Kung University Hospital:
ESRD
Diabetes mellitus
Endothelial progenitor cells
Blood flow
Hemodialysis

Additional relevant MeSH terms:
Arteriovenous Malformations
Fistula
Kidney Diseases
Diabetes Mellitus
Arteriovenous Fistula
Kidney Failure, Chronic
Pathological Conditions, Anatomical
Urologic Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Malformations
Cardiovascular Abnormalities
Cardiovascular Diseases
Vascular Fistula
Vascular Diseases
Congenital Abnormalities
Renal Insufficiency, Chronic
Renal Insufficiency
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014